Determining the Clinical Impact and Prevalence of Hemorrhagic Subtypes in Perimesencephalic Subarachnoid Hemorrhage

Background: Perimesencephalic subarachnoid hemorrhage (pmSAH) is a distinct subtype of traumatic subarachnoid hemorrhage (SAH) characterized by a localized bleeding pattern around the midbrain not resulting from a ruptured aneurysm of a posterior circulation main artery. Traditionally considered benign with generally good prognosis, pmSAH has been attributed to a presumed venous etiology. However, recent advances in imaging technology have led to the identification of previously occult vascular lesions, most notably basilar artery perforator aneurysms (BAPAs) that may present a potential cause in a subset of patients with pmSAH. Preliminary data from the international PERFAN registry which retrospectively included 148 patients with ruptured BAPAs, challenge the benign perception of pmSAH as a whole. Interestingly, in this biggest case collection so far, patients diagnosed with BAPAs experienced significantly higher rates of complications and worse functional outcomes compared to cases of non-aneurysmal pmSAH (NA-pmSAH). To date, prospective data on prevalence, presentation and outcome of BAPA-associated pmSAH (BAPA-pmSAH) is missing, thus complicating decisions on management of this increasingly diagnosed entity. Aims: The DECIPHER-pmSAH study aims to establish a prospective registry to: 1. determine and compare the prevalence of BAPA-pmSAH and non-aneurysmal pmSAH 2. compare short-term and mid-term functional outcomes between patients with BAPA-pmSAH and those with non-aneurysmal pmSAH 3. evaluate the rate and nature of complications in both these pmSAH subgroups 4. enhance the understanding of radiological features associated with pmSAH, with the aim of distinguishing between BAPA-pmSAH and non-aneurysmal pmSAH 5. characterize observed treatment strategies and their outcomes, comparing conservative and active management approaches Design: The DECIPHER-pmSAH is a prospective, multicenter, observational study. For an adequately powered study, we are aiming at enrollment of at least 264 patients over the course of three years, starting on January 1st, 2026. For recruiting participating sites, we are aiming to build upon the previously established collaboration with multiple international centers contributing to the PERFAN registry, in which cases of perforator aneurysms were retrospectively collected. Methods: This study will include cases of atraumatic pmSAH where no aneurysm of main arteries of the posterior circulation was detected. Predefined diagnostic workup criteria must be met for patient enrollment, including cross-sectional imaging (CT or MRI) at baseline, whenever possible and clinically justified at least one digital subtraction angiography (DSA) with high-resolution three-dimensional rotational angiography (3D-RA) and collection of clinical data at index presentation, hospital discharge and 90 days follow-up. Anonymized imaging data will be centrally analyzed by trained neuroradiologists, blinded to clinical data in a core lab at the Inselspital, Bern. The primary endpoint to be examined is the prevalence of ruptured BAPA and non-aneurysmal hemorrhage in cases of pmSAH. Secondary and tertiary endpoints include clinical outcomes at 90 days after index presentations and specific radiological findings respectively.

Inclusion Criteria: * Patients aged ≥18 years with a non-traumatic pmSAH or limited additional blood in adjacent cisterns (pmSAH "plus") * Cross-sectional imaging at baseline (CT or MRI) * Written informed consent for study participation was obtained. Exclusion Criteria: * Presence of documented written or verbal refusal * pmSAH patients with a presumed traumatic source * Saccular/fusiform aneurysm of the main arteries of the posterior circulation (e.g. V4, AICA, PICA, basilar trunk, basilar tip) * pmSAH patients with a shunting lesion in the vertebrobasilar territory (i.e. brain AVM, brain/spine AVF) * pmSAH patients with a cavernous malformation in the posterior fossa * Basilar artery perforator aneurysm group (BAPA group): * Aneurysm arising from the basilar artery trunk adjacent to a perforating branch but not involving a perforating artery (Satti Type 1) * Flow-related BAPA (i.e. AVM, AVF) * Severely impaired renal function defined as KDIGO grade 4 (GFR \